Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H19ClFNO4S |
Molecular Weight | 435.896 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(=O)(=O)C1=C2N(CC3=CC=C(Cl)C=C3)C4=C(CC[C@@H]4CC(O)=O)C2=CC(F)=C1
InChI
InChIKey=NXFFJDQHYLNEJK-CYBMUJFWSA-N
InChI=1S/C21H19ClFNO4S/c1-29(27,28)18-10-15(23)9-17-16-7-4-13(8-19(25)26)20(16)24(21(17)18)11-12-2-5-14(22)6-3-12/h2-3,5-6,9-10,13H,4,7-8,11H2,1H3,(H,25,26)/t13-/m1/s1
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdfCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17300164 | https://www.ncbi.nlm.nih.gov/pubmed/19748656
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000889/WC500042219.pdf
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/17300164 | https://www.ncbi.nlm.nih.gov/pubmed/19748656
Laropiprant is a drug, which was used in combination with nicotinic acid (also known as niacin) and was known under tradename: tredaptive. Tredaptive was indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia. The marketing authorisation for Tredaptive has been withdrawn at the request of the marketing-authorisation holder due to increases in side effects with no cardiovascular benefit. Laropiprant is a selective antagonist of the prostaglandin D(2) (PGD(2)) receptor subtype 1 (DP1). It also has the affinity to interact with thromboxane A2 receptor (TP), although it is approximately 190-fold less potent when compared to DP1. Activation of TP has been shown to induce platelet aggregation in vitro, whereas activation of human platelet DP1 inhibits platelet aggregation. These in vitro data indicate that laropiprant may alter platelet function either by enhancement of platelet reactivity through DP1 antagonism or by inhibition of platelet aggregation through TP antagonism. Also were clinical trials phase II for the laropiprant alone, there were shown, that drug did not demonstrate efficacy in asthmatic patients or patients with allergic rhinitis.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL4427 |
0.09 nM [IC50] | ||
Target ID: Q13258 Gene ID: 5729.0 Gene Symbol: PTGDR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17300164 |
0.57 nM [Ki] | ||
Target ID: CHEMBL4427 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17300164 |
0.57 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Palliative | Tredaptive Approved UseTredaptive is indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia: who are treated with a statin and could benefit from having Tredaptive added to their regimen, in whom a statin is considered inappropriate or not tolerated |
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Palliative | Tredaptive Approved UseTredaptive is indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia: who are treated with a statin and could benefit from having Tredaptive added to their regimen, in whom a statin is considered inappropriate or not tolerated |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Gateways to clinical trials. | 2007 Dec |
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Metabolism of MK-0524, a prostaglandin D2 receptor 1 antagonist, in microsomes and hepatocytes from preclinical species and humans. | 2007 Feb |
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Gateways to clinical trials. | 2007 Oct |
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Targeting multiple dyslipidemias with fixed combinations--focus on extended release niacin and simvastatin. | 2008 |
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Gateways to clinical trials. | 2008 Apr |
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Nicotinic acid: recent developments. | 2008 Jul |
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Gateways to clinical trials. July-August 2008. | 2008 Jul-Aug |
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Gateways to clinical trials. | 2008 Jun |
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Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. | 2008 Mar 1 |
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Gateways to clinical trials. | 2008 May |
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Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors. | 2008 Nov |
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Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia. | 2009 |
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Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin. | 2009 |
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Laropiprant in combination with extended-release niacin does not alter urine 11-dehydrothromboxane B2, a marker of in vivo platelet function, in healthy, hypercholesterolemic, and diabetic subjects. | 2009 Dec |
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Blood pressure-lowering effects of extended-release niacin alone and extended-release niacin/laropiprant combination: a post hoc analysis of a 24-week, placebo-controlled trial in dyslipidemic patients. | 2009 Jan |
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Niacin: an old drug rejuvenated. | 2009 Jan |
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Does nicotinic acid (niacin) lower blood pressure? | 2009 Jan |
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Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. | 2009 Jul 1 |
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Lipid-modifying efficacy of extended release niacin/laropiprant in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia. | 2009 May-Jun |
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High-density lipoprotein cholesterol: current perspective for clinicians. | 2009 Oct-Nov |
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The mechanism and mitigation of niacin-induced flushing. | 2009 Sep |
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Pharmacokinetics of laropiprant and glucuronide metabolite in patients with severe renal insufficiency. | 2009 Sep-Oct |
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Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia. | 2010 |
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Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia. | 2010 Apr 15 |
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Nicotinic acid + larodiorant. Laropiprant adds its own adverse effects. | 2010 Feb |
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Niacin, an old drug with new perspectives for the management of dyslipidaemia. | 2010 Jan-Feb |
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High density lipoproteins-based therapies for cardiovascular disease. | 2010 Jul |
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[Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: non-pharmacological and pharmacological approaches]. | 2010 Jul |
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Niacin and laropiprant. | 2010 Jun |
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Low high-density lipoprotein cholesterol: current status and future strategies for management. | 2010 Oct 29 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00664287
niacin/laropiprant 1 g/20 mg daily. After 4 weeks, niacin/laropiprant will be increased to 2 g/40 mg for remainder of study.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22870195
In vitro treatment of platelets with laropiprant (1 µmol/L) prevented the inhibitory effects of PGD(2) on platelet function, i.e. platelet aggregation, Ca(2+) flux, P-selectin expression, activation of glycoprotein IIb/IIIa and thrombus formation. At higher concentrations, 10 µmol/L laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation, Ca(2+) flux, P-selectin expression, and activation of glycoprotein IIb/IIIa.
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C26170
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m6696
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C518174
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CHEMBL426559
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ACTIVE MOIETY